Hepatitis C

Hepatitis means inflammation of the liver. The liver is a one of the most vital organs in the body that processes nutrients, filters the blood, and fights infections. Hepatitis causes damages to the liver and compromises these important bodily functions. Hepatitis has many causes including heavy alcohol use, certain medical conditions and medications, some bacterial and parasitic infections, but it is most commonly caused by a virus infection. Several different viruses, named the Hepatitis A, B, C, D, and E viruses, can cause viral hepatitis.

Hepatitishepatitis-c

Viral-Hepatitis

Hepatitis C is an infection of the liver by the Hepatitis C virus (HCV). The first several months after someone is infected by the HCV is referred to as the acute phase of the infection or Acute Hepatitis C. Most people (approximately 70%–80%) with acute Hepatitis C do not have any symptoms, but some people can exhibit symptoms that range from mild to extremely severe that requires hospitalization soon after being infected, including:

  • Fever
  • Fatigue
  • Loss of appetite
  • Nausea
  • Vomiting
  • Abdominal pain
  • Dark urine
  • Clay-colored bowel movements
  • Joint pain
  • Jaundice (yellow color in the skin or eyes)

For reasons that are currently unknown, approximately 20% of people are able to self-clear the HCV during the first 6 months of infection without receiving any treatments. Unfortunately, for the rest, the HCV stays in the liver and a chronic life-long infection develops. Over time, chronic Hepatitis C continuously causes damages to the liver leading to serious health problems including liver diseases, cirrhosis (severe scarring/hardening of the liver), liver failure, and even liver cancer. It is estimated 130–150 million people globally have chronic hepatitis C infection. A significant number of those who are chronically infected will develop liver cirrhosis or liver cancer and approximately 500,000 people die each year from hepatitis C-related liver diseases.

course of illness with hepatitis c

Transmission of Hepatitis C

HCV is primarily spread by blood-to-blood contact. Today, most transmissions of HCV are associated with sharing needles or other equipment in intravenous drug use or poorly sterilized medical equipment and needle-stick injuries in healthcare. Before 1992, when widespread screening of the blood supply began in the United States, Hepatitis C was also commonly spread through blood transfusions and organ transplants. HCV can also be transmitted sexually and can be passed from an infected mother to her baby; however these modes of transmission are much less common.

Hepatitis C has often been called a silent disease because most people with hepatitis C often have no symptoms. The CDC (Centers for Disease Control and Prevention) recommends HCV testing for anyone with increased risks for HCV infection, these include:

  • Persons born from 1945 through 1965
  • Persons who have ever injected illegal drugs, including those who injected only once many years ago
  • Recipients of clotting factor concentrates made before 1987
  • Recipients of blood transfusions or solid organ transplants before July 1992
  • Patients who have ever received long-term hemodialysis treatment
  • Persons with known exposures to HCV, such as
    • health care workers after needlesticks involving HCV-positive blood
    • recipients of blood or organs from a donor who later tested HCV-positive
  • All persons with HIV infection
  • Patients with signs or symptoms of liver disease (e.g., abnormal liver enzyme tests)
  • Children born to HCV-positive mothers (to avoid detecting maternal antibody, these children should not be tested before age 18 months)

Testing for Hepatitis C

The initial screening test is a blood test called the Hepatitis C antibody Test (anti-HCV),  that looks for antibodies to the HCV.

  • non-reactive or negative antibody test means that a person is not currently infected with the hepatitis C virus.
  • reactive or positive antibody test means a person has been infected with the hepatitis C virus at some point in time. It does not tell you whether your infection is new, how long you have had it, or if the infection is still present.

If the hepatitis C antibody test is reactive, a HCV RNA test is needed to determine if the person still has the virus and how much of the virus is in his/her blood (viral load). If the Hepatitis C RNA test is:

  • Negative—this means a person was infected with hepatitis C, but the virus has now been cleared from his or her body. This person is no longer infected.
  • Positive—this means a person has Hepatitis C and is currently infected.

HCV genotyping – this test identifies the type (or genotype) of the hepatitis C virus you have. There are six genotypes of HCV, numbered from 1 to 6, and you can be infected with more than one genotype at the same time. In North America, genotype 1 is the most common.

Treatment for Hepatitis C

The goal of treatment is to eradicate hepatitis C virus (HCV) RNA, which is predicted by the achievement of a sustained virologic response (SVR), defined by the absence of HCV RNA by polymerase chain reaction three to six months after stopping treatment. An SVR is associated with a 99 percent chance of being HCV RNA negative during long-term follow-up and can therefore be considered cure of the HCV infection.

The standard of care for hepatitis C is changing rapidly. Until recently, hepatitis C treatment was based on therapy with interferon and ribavirin, which required weekly injections for 48 weeks, cured approximately half of treated patients, but caused frequent and sometimes life-threatening adverse reactions. Recently, new antiviral drugs have been developed. These medicines, called direct antiviral agents (DAA) are much more effective, safer and better-tolerated than the older therapies. Therapy with DAAs result can cure most persons with HCV infection and treatment is shorter (usually 12 weeks) and much safer.

In October 2013, US FDA unanimously voted to recommend approving Sovaldi (Sofosbuvir) by Gilead Sciences Inc. for use in patients with Hepatitis C. Sofosbuvir is the first all-oral option for patients with HCV. It is a game-changer and will allow high cure rates, with just 12 week regimens. It can eradicate HCV without interferon being part of the treatment cocktail. Efficacy has been established in HCV genotype 1-4 including those with hepatocellular carcinoma and HCV/HIV co-infection. No viral resistance to sofosbuvir was detected among patients who relapsed following completion of therapy.

For patients with chronic genotype 1 HCV infection who are initiating antiviral therapy, an interferon-free regimen instead of an interferon-containing regimen is strongly recommended (Grade 1A). Interferon-free regimens achieve cure rates of approximately 95 percent or higher and are well tolerated, without the well-known toxicity associated with interferon. Although the production cost of DAAs is low, the initial prices are very high and make access to these drugs very difficult even in high-income countries.

Hepatitis C Treatment Summary

Based on Guidelines for the management of HCV infection released jointly by the American Association for the Study of Liver Diseases and Infectious Diseases Society of America (AASLD and IDSA) in 2014 which are updated on a continuous basis following availability of new medications or release of major treatment trials. Other guidelines include treatment recommendations from the European Association for the Study of the Liver (EASL) updated in 2015, and United Kingdom consensus guideline updated in 2014, and World Health Organization (WHO) guidelines released in 2014 on screening and treatment of HCV.

Genotype Treatment Regimen Treatment Duration Cure Rate
Non-Cirrhosis Cirrhosis
Genotype 1 Epclusa (Sofosbuvir + Velpatasvir) 12 weeks *12-24 weeks 98%
Harvoni (Sofosbuvir + Ledipasvir) 24 weeks 94-98%
Sofosbuvir + Daclatasvir 98% Type 1a
99% Type 1b
Sofosbuvir + Ribavirin 90-95%
Genotype 2 Epclusa (Sofosbuvir + Velpatasvir) 12 weeks *12-24 weeks 99%
Sofosbuvir + Daclatasvir 24 weeks 98%
Sofosbuvir + Ribavirin 93-95%
Genotype 3 Epclusa (Sofosbuvir + Velpatasvir) 24 weeks *12-24 weeks 95%
Sofosbuvir + Daclatasvir 24-48 weeks 94%
Sofosbuvir + Ribavirin 93%
Genotype 4 Epclusa (Sofosbuvir + Velpatasvir) 12 weeks 24 weeks 100%
Harvoni (Sofosbuvir + Ledipasvir) 93%
Sofosbuvir + Daclatasvir 93%
Sofosbuvir + Ribavirin 90-96%
Genotype 5 Epclusa (Sofosbuvir + Velpatasvir) 12 weeks *12-24 weeks 97%
Harvoni (Sofosbuvir + Ledipasvir) 24 weeks 93%
Genotype 6 Epclusa (Sofosbuvir + Velpatasvir) 12 weeks *12-24 weeks 100%
Harvoni (Sofosbuvir + Ledipasvir) 24 weeks 96%

*For patients with advanced cirrhosis and Hep C genotype 1–6, Epclusa + ribavirin provides an all-oral treatment option for 12 weeks of therapy.

Hepatitis C DAAs mechanisms of action

DAA Mechanisms

Epclusa (Sofosbuvir + Velpatasvir)

  • Approval Status: FDA approved on June 28, 2016
  • Indication for all HCV genotypes 1,2,3,4,5,6
    – First line therapy in USA and Canada
    – Without cirrhosis or with compensated cirrhosis (Child-Pugh class A): one tablet once daily for 12 weeks
    – With decompensated cirrhosis (Child-Pugh class B or C): one tablet once daily with concomitant ribavirin for 12 weeks.
  • Class & Mechanism:
    – Sofosbuvir: Nucleotide analog NS5B Polymerase inhibitor
    – Velpatasvir: NS5A inhibitor
  • Dosing: Sofosbuvir 400mg + Velpatasvir 100 mg combo tablet PO once daily
  • Adverse Effects (AE) attributable to Epclusa
    – Fatigue, headache, insomnia, nausea, and diarrhea
  • Wholesaler Acquisition Cost in United States
    – estimated 12-week cost = $74,760

Harvoni (Sofosbuvir + Ledipasvir)

  • Approval Status: FDA approved on Oct 10, 2014
  • Indication for HCV genotype 1, 4, 5, 6
    – First line therapy in USA and Canada
    – Recommended for treatment naïve & relapse HCV, cirrhotic patients, hepatocellular carcinoma, HIV and HCV co-infection
    – Non-cirrhotic patients: 12 weeks Cirrhotic patients: 24 weeks
  • Class & Mechanism:
    – Sofosbuvir: Nucleotide analog NS5B Polymerase inhibitor
    – Ledipasvir: NS5A inhibitor
  • Dosing: Sofosbuvir 400mg + Ledipasvir 90 mg combo tablet PO once daily
  • Adverse Effects (AE) attributable to Harvoni
    – Fatigue, headache, nausea
  • Wholesaler Acquisition Cost in United States
    – estimated 12-week cost = $94,500

Sovaldi (Sofosbuvir)

  • Approval Status: FDA approved on December 6, 2013
  • Indication for HCV and HCV-HIV Coinfection
    – Genotype 1,2, 4: Sofosbuvir (12 weeks) – Genotype 3: Sofosbuvir (24 weeks)
    – Hepatocellular carcinoma and awaiting transplant: Sofosbuvir (up to 48 weeks)
  • Class & Mechanism: Nucleotide analog NS5B polymerase inhibitor
  • Dosing: 400 mg PO once daily with or without food
  • Adverse Effects (AE) attributable to Sofosbuvir
    – Fatigue, headache, nausea
  • Wholesaler Acquisition Cost in United States
    – estimated 12-week cost = $84,000

Daklinza (Daclatasvir)

  • Approved by United States FDA July 24, 2015
  • Indicated with sofosbuvir, with or without ribavirin for the treatment of chronic HCV genotype 1 and 3 in adults
  • Class & Mechanism: NS5A inhibitor
  • Dosing Preparations and Adjustments:
    – Daclatasvir 60 mg and 30 mg tablets
    – No dosage adjustment with any degree of renal impairment
    – No dosage adjustment with mild, moderate, or severe hepatic impairment
  • Most Common Adverse Effects:
    – Headache, fatigue, nausea, diarrhea

Blogs About Hepatitis C

For further information about Hepatitis C and its treatment using Sovaldi (Sofosbuvir), Daclatasvir (Daklinza), Harvoni (Sofosbuvir+Ledipasvir), and Epclusa (Sofosbuvir + Velpatasvir) please consult our pharmacists at toll free number 1-888-488-9965.

Last modified on